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Reproductive Hormones in the Regulation of Apoptosis of Neutrophils

S. V. Shirshev1, E. M. Kuklina1*, and A. A. Yarilin2

1Institute of Ecology and Genetics of Microorganisms, Ural Division, Russian Academy of Sciences, ul. Goleva 13, Perm 614081, Russia; fax: (3422) 446-711; E-mail: conf@ecology.psu.ru

2State Research Center - Institute of Immunology, Ministry of Health of Russia, Kashirskoe Shosse 24, Moscow 115478, Russia

* To whom correspondence should be addressed.

Received March 23, 2002; Revision received May 14, 2002
The ability of main reproductive hormones such as chorionic gonadotropin (CG), estradiol, and progesterone to regulate apoptosis of human neutrophils was studied. The hormones were studied separately and in physiological combinations specific for different trimesters of pregnancy. A low dose of CG (10 IU/ml) increased the spontaneous apoptosis of neutrophils, whereas its combination with estradiol and progesterone corresponding to that of trimester III of pregnancy significantly decreased this parameter. The stimulating effect of CG was prevented by an inhibitor of protein kinase A, whereas the hormone-induced suppression of apoptosis depended on the activity of Ca2+-channels. The antiapoptotic effect of the hormonal combination corresponding to that of trimester III was also manifested in the presence of autologous T-lymphocytes and on stimulation of neutrophils by bacterial lipopolysaccharide. The apoptosis induced with monoclonal antibodies to CD95 was significantly suppressed by the hormones studied and their combinations. Thus, apoptosis of neutrophils is effectively regulated by reproductive hormones; this seems to be an important control mechanism of activation of these cells in pregnancy.
KEY WORDS: apoptosis, neutrophils, T-lymphocytes, chorionic gonadotropin, estradiol, progesterone, pregnancy